Process of producing phenylalkylhydrazines



United States Patent PROCESS OF PRODUCING PHENYLALKYL- HYDRAZINES JohnH. Biel, Milwaukee, Wis., assignor,'by mesne assrg nments, to LakesideLaboratories, Inc., Milwaukee, W1s., a corporation of Delaware NoDrawing. Filed Nov. 21, 1958, Ser. No. 775,360 7 Claims. (Cl. 260-3405)This invention relates to the production of phenylalkylhydrazines. Moreparticularly, this invention is concerned with a novel process ofproducing phenylalkylhy-.

drazines. v

This application is' a continuation-in-part of Serial No.

605,724 filed Augst 23, 1956, now abandoned, Serial No.

716,876 filed February 24, 1958, and Serial No. 716,877 filed February24, 1958, now abandoned, wherein it is shown that phenylalkylhydrazonesmay be'redu'ced by chemical or catalytic means to the correspondingphenylalkylhydrazines. While the conventional reduction meth- Ods leadto the desired product, low yields are ordinarily obtained due to theformation of large amounts of undesirable by-products. This may beillustrated by the reduction of 1-phenyl-2-propyl hydrozone (I) tol-phenyl-2-propyl hydrazine (III) according to the following scheme:

[Phonic (CH )=N-]z (II) by-product PhCH2CH(CH3)NH-NH2 (III) desiredPhCHzC=NNHz-+ (7H3 [H] [PhOH;OH(CH;)-NH]= (IV) lay-product.

I Ph OH2CH (C H:)NH (V) by-product Ithas been found that large amountsof II also occur, besides the desired product, when the reductionproceeds slowly and incompletely with catalysts such as palladium,

R1 R to the corresponding phenylalkylhydrazines of the for may bereadily effected by hydrogen using platinum or platinum oxide as thecatalyst in a lower alcohol as solvent and in the presence of addedglacial acetic acid, wherein Z represents a bond or a straight orbranched lower alkylene group, R represents hydrogen or a lower alkylgroup, provided however that Z is only a branched alkylene when R ishydrogen and that R is only a lower alkyl group when Z is a bond, and Ris hydrogen or one or more substituents on the phenyl group such as alower alkyl group like the methyl, ethyl, propyl and butyl groups, alower alkoxy group such as the methoxy, ethoxy and propoxy groups, anaryl group such as the phenyl group, an aralkyl group and particularly aphenylmula t 2,978,461 I Patented Apr-.4, 9 6 1 lower alkyl group suchas where z-cu contains 5 carbons'or less Some of thephenylalkylhydrazones which may duced according to this processare'phenyl-2-propylidenyl hydrazine,N-(3-phenyl-2-propylideriyl)hydrazinefiN-[B-T (3 ,4-methylenedioxyphenyl2 propylidenyl] hydrazine, 6- phenyl-2-hexylidenyl liydrazine,4-(p-chlorophenyl);-3-

butylidenyl hydrazine, 4-(p-hydroxyphenyl)-2-butyliden I.

yl hydrazine, and l-phenyl-l-methyl-methylidenyl hydrazine. Platinum andplatinum oxide' may be employed in the process in a .finely dividedstate. In addition, these catalysts may also be used satisfactorily onsuitable catalyst carriers.

Although any of the lower alkanols may be employed as the solvent,including methanol, ethanol, isopropanol and t-butanol, the solventadvisably employed is ethanol.

Denatured ethanol is also satisfactory for the reaction. medium. Thepresence of water is undesirable and;

should be avoided.

The hydrogen pressure for the reduction is not criti cal. For smallbatches, such as 0.50 mole, pressures of about p.s.i. are satisfactory.In large-scale manufacture, however, it is advisable to usepressuresof'about 1,500 to 3000 psi.

Hydrogenation temperatures above 80 C. are advis ably not employed sincehigher temperatures favor cleavage of the hydrazine N-N linkage to formcompound V. In general, from room temperature (20 C.) to about 50 C. ispreferred for the hydrogenation. p

The amount of glacial acetic acid included in the i solvent medium isnot narrowly criticalalthough sufiicient acetic acid should be added toreact with.a1l of the hydrazone to be reduced. =Thus, advisably at leastone mole of glacial acetic acid should be added for each mole ofphenylalkyl hydrazone to be reduced.

The hydrogenation is terminated when hydrogen 'uptake has substantiallyceased. The reaction mixture, is

then filtered to remove the catalyst and the filtratejheatr ed to removethe solvent and acetic acid. After making the residue strongly alkaline,as with solid potassiurm hydroxide, the desired product may be extractedwith ether and recovered by fractional distillation.

By following the procedure of this invention the desired product isobtained in yields of 55% to 70% although from 30% to 45% yields ofby-products II and iv are still obtained. a

Some of the phenylalkylhydrazines which may spendingphenylalkylhydrazones are 1-phenyl-2-propyl phenyl-4-hexyl hydrazine.

The following examples are presented to illustratethe invention.

EXAMPLE 1 l-phenyl-Z-propyl hydrazin the benzyl group, a phenyl loweralkoxy groupsuch as phenylmethoxy and'including the phenoxy group, thehydroxy group, polyalkoxy" substituents such as dimethoxy and trimethoxysubstit uents, a lower alkylenedioxy group such as'themethylene dioxygroup,ja halogen such as bromine of chlorine, and 1 a dihydroxy group.The reduction is particularly useful;

bar duced according to this process by'reduction of the correat ests;

tion and the solvent andaceticacid were distilled. The; residue wastaken up in water and madestrongly alkaline by the addition. oi solidpotassiumhydroxide. The alkaline mixture was extracted with ether andthe ether extracts dried with potassium carbonate. The product wascollected by fractional distillation, B.P. 85 C. (0.30 mm); yield 512 g.(68%). N 1.5375.

Analysis.Calcd. for C H N N, 18.66; Found: N, 18.74.

The hydrochloride salt was formed in a mixture of 1 10 isopropylalcohol: diisopropyl ether and. recrystallized from acetonitrile,yield.87%, M-.P. 124-125 C.

Analysis.-Calcd, for C H' CIN Cl, 18.99; N, 15.01. Found: Cl, 19.00; N,15.16.

EXAMPLE 2 Z-phenyI-S-propyl hydrazine Alphq-e thylbenzyl hydrazine CgHsPropiophenone hydrazone was reduced with platinum oxide in ethanolcontaining a molar equivalent'of glacial acetic acid according to theprocedure of Example2.

EXAMPLE 4 I-(3,4-methylenedioxyphenyl)-2-propyl hydrazine1-(3,4-methylenedioxyphenyl)-2-propylidenyl hydrazine was reduced inethanol containing a molar equivalent of glacial acetic acid withplatinum oxide with hydrogen at 60 p.s.i. and starting at roomtemperature as in Example 2.

EXAMPLE 5 l-phenyl-Z-propyl hydrazine The procedure of Example 1 wasrepeated using isopropanol in place of ethanol and a yield of about 60%obtained.

Various changes and modifications of the invention can be made and, tothe extent that such variations incorporate the spirit of thisinvention, they are intended to be included within the scope of theappended claims.

4 What is claimed is: 1. The process which comprises reducing a compoundof the formula Z.i=,,N-NH2 HI in a dry lower alkanolcontaining at leasta molar equivalent of acetic acid-per amount of hydrazone present;

with-hydrogen using as.a catalyst amember of the. group consisting ofplatinum and platinum-oxide at a temperature from. 20 C. to. C. to.produce a, compound of the formula wherein Z is a member of the groupconsisting of a single chemical bond and straight and branched loweralkylene groups, R is a member of the group consisting of hydrogen andlower alkyl groups, and Z is only a branched alkylene when R is hydrogenand R is only a loweralkyl group when Z is a chemical bond, and R is amember of the group consisting of hydrogen and nuclear substituents onthe phenyl group.

2. The process of claim 1 in which the hydrogenation is carried out inethanol..

3. The process which comprises reducing l-phenyl-Z- propyl hydrazonewith hydrogen using a catalyst of the group consistingofplatinum'andplatinum oxide in a lower alkanol containing acetic acidin an amount at least molecularly equivalent to the hydrazone present ata temperature from 20 C. to 80 C. to produce l-phenyl- 2-propylhydrazine.

4. The process which comp ises reducing 2-phenyl-3- propylidenylhydrazine with hydrogen using a catalyst of the group consisting ofplatinum and platinum oxide in a lower alkanol containing aceticacid inan amount at least molecularly equivalent to the hydrazone present at atemperature from 20" C. to 80 C; to produce 2-phenyl-3-propyl hydrazine.

5. T he'processwhich comprises reducing propiophenone hydrazone withhydrogen using a catalyst of the group consisting of platinum andplatinum oxide in a lower alkanol containing acetic acid in an amount atleast molecularly equivalent to the hydrazone present at a temperaturefrom 20 C. to 80 C. to produce alphaethyl benzyl hydrazine.

6. The process which comprises reducing1-(3,4-methylenedioxyphenyl)-2-propylidenyl hydrazine with hydrogenusing a catalyst of the group consisting of platinum and platinum oxidein a lower alkanol containing acetic acid in an amount at leastmolecularly equivalent to the hydrazone present at a temperature from 20C. to 80 C. to produce 1(3,4-methylenedioxyphenyl)-2-propyl hydrazine.

7. The process of claim 3 in which the alkanol is ethanol.

References Cited in the file of this patent Taipale:Berichte Deut.Chem., vol. 56, pages 954 962 (1923).

Taipale: Chemical Abstracts, vol. 17, pages 3015- 3016 (1923).

Klages et al.: Annalen der Chemie, vol. 547, p. 8 (1941).

1. THE PROCESS WHICH COMPRISES REDUCING A COMPOUND OF THE FORMULA
 6. THEPROCESS WHICH COMPRISES REDUCING1-(3,4-METHYLENEDIOXYPHENYL)-2-PROPYLIDENYL HYDRAZINE WITH HYDROGENUSING A CATALYST OF THE GROUP CONSISTING OF PLATINUM AND PLATINUM OXIDEIN A LOWER ALKANOL CONTAINING ACETIC ACID IN AN AMOUNT AT LEASTMOLECULARLY EQUIVALENT TO THE HYDRAZONE PRESENT AT A TEMPERATURE FROM20*C. TO 80* C. TO PRODUCE 1-(3,4-METHYLENEDIOXYPHENYL)-2-PROPYLHYDRAZINE.